Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor

NCT01068769 | Completed Phase 2 Results DMC

• 1 other identifier: 09-400
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this research study is to determine the safety and activity of regorafenib in participants with advanced gastrointestinal stromal tumor (GIST) if the standard approved therapies, imatinib and sunitinib, have failed to control the disease. Regorafenib is a drug that blocks abnormally active signaling enzymes called "tyrosine kinases" which are important to the growth of GIST. This "tyrosine kinase inhibition" is similar to the way that both imatinib and sunitinib work; however, regorafenib blocks certain additional signaling pathways that are not blocked by imatinib or sunitinib. Regorafenib has been not been tested in GIST participants before this research study.

Conditions

Gastrointestinal Stromal Tumor

Keywords

regorafenib; GIST

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit as Defined by the Composite of Complete Response, Partial Response and Stable Disease Lasting 16 Weeks or More Per RECIST 1.1 as a Measure of Disease Control

  The composite of complete response, partial response, and stable disease lasting 16 weeks or more per RECIST 1.1 as a measure of disease control. This is for target lesions. Complete response is disappearance of all target lesions and partial response is \>+30% decrease in the sum of the longest diameter of target lesions. Stable disease is neither shrinkage by greater than or equal to 30% of the sum of the longest diameter of target lesions or the increase of lesions by greater than or equal to 20% of the sum of the longest diameter of target lesions. Progressive disease is considered an increase of the sum of the longest diameter of target lesions by greater than or equal to 20%.

  2 years

Secondary Outcomes (1)

• Progression-free Survival (PFS)

  From date of enrollment until date of first documented progression or date of death from any cause, whichever came first

Study Arms (1)

Regorafenib

EXPERIMENTAL

Regorafenib adminstered orally, 160 mg per day on days 1 through 21 of a 28 day cycle

Drug: regorafenib

Interventions

regorafenib DRUG

Taken orally, once a day in the morning for 3 weeks followed by a one week rest period

Also known as: Stivarga

Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age at the time of study entry
• Histologically confirmed metastatic and/or unresectable GIST with prior failure of both conventional tyrosine kinase inhibitors, imatinib and sunitinib.
• Measurable disease per RECIST 1.1. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion.
• ECOG Performance Status 0 or 1
• Adequate organ and marrow function as outlined in the protocol
• Fully recovered from the acute effects of prior cancer therapy before initiation of study drug
• Patients must be suitable for oral drug administration
• Willingness to use effective means of birth control throughout the duration of clinical study and for at least 3 months after completion of study drug
• Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of study drug administration

You may not qualify if:

• Use of any unapproved tyrosine kinase inhibitors or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study drug
• Participants who have had radiotherapy within 4 weeks prior to study entry
• Major surgery, or significant traumatic injury within 4 weeks prior to study entry
• Presence of symptomatic or uncontrolled brain or central nervous system metastases
• Prior exposure to sorafenib
• Prior exposure to regorafenib
• Known or suspected allergy to the investigational agent or any agent given in association with this trial
• Individuals with a history of a different malignancy, other than cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy or other primary malignancy is neither currently clinically significant nor requiring active intervention
• Clinically significant cardiac arrhythmias and/or patients who require anti-arrhythmic therapy (excluding beta blockers or digoxin)
• History of clinically significant cardiac disease or congestive heart failure \> NYHA class 2. Patients must not have unstable angina or new-onset angina within the last 3 months or myocardial infarction within the past 6 months
• Hypertension as defined by systolic blood pressure 140-159 mmHg or diastolic blood pressure 90-99 mmHg; recurrent or persistent or symptomatic increase by \> 20 mmHg (diastolic) or to systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg if previously within normal limits, despite optimal medical management
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication
• Ongoing infection of Grade 3 or higher
• Patients with evidence of, or history of, bleeding diathesis. Any major hemorrhage or bleeding event of Grade 3 or higher within 4 weeks of start of study medication
• Non-healing wound, ulcer or bone fracture

Sponsors & Collaborators

• Suzanne George, MD: lead
• Brigham and Women's Hospital: collaborator
• Massachusetts General Hospital: collaborator
• Fox Chase Cancer Center: collaborator
• Oregon Health and Science University: collaborator
• Bayer: collaborator

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (1)

• Ben-Ami E, Barysauskas CM, von Mehren M, Heinrich MC, Corless CL, Butrynski JE, Morgan JA, Wagner AJ, Choy E, Yap JT, Van den Abbeele AD, Solomon SM, Fletcher JA, Demetri GD, George S. Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy. Ann Oncol. 2016 Sep;27(9):1794-9. doi: 10.1093/annonc/mdw228. Epub 2016 Jul 1.

  PMID: 27371698 DERIVED

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Results Point of Contact

• Title: Dr. Suzanne George
• Organization: Dana-Farber Cancer Institute

sgeorge2@partners.org

617-632-5204

Study Officials

• Suzanne George, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Director Center for Sarcoma and Bone Oncology

Study Record Dates

• First Submitted: February 12, 2010
• First Posted: February 15, 2010
• Study Start: February 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: August 1, 2020
• Last Updated: August 24, 2020
• Results First Posted: February 24, 2014

Record last verified: 2020-08

Locations

US (4)